The overall goal of this proposal is to elucidate the mechanisms which regulate immune senescence. Immune senescence is reflected primarily in the loss of replicative potential of T cells from aged humans. This is the result of both a failure of activated T cells to progress through the G1 phase of the cell cycle in response to the essential growth factor Interleukin 2 and a failure of some cells to become activated and progress from G0 to G1 following the interaction with a mitogen such as the anti-D3 monoclonal antibody OKT3. Transmembrane signaling via the IL2 receptor and the CD3-antigen receptor complex involve similar intracellular pathways which lead to the activation of genes associated with proliferation. The specific aims of the proposal are: 1. To determine whether a failure of activated T cells from aged humans to progress through the cell cycle in response to IL2 is due to impaired signal transduction via the IL2 receptor. 2. To determine whether a failure of T cells from aged humans to become activated in response to OKT3 binding is due to impaired signal transduction via the CD3-antigen receptor. 3. To determine whether a failure to transduce cell surface signals results in an alteration in the defined pathway of transcription associated with T cell proliferation.